Genetic and physical mapping techniques will he used to isolate the gene for Primary Congenital Glaucoma (PCG). PCG is an autosomal recessive disorder with neonatal clinical onset. It is caused by unknown developmental defect(s) of the trabecular meshwork and the anterior chamber angle. Nothing is known about its chromosomal location, and no satisfactory therapy is available. The main linkage approach to mapping the PCG gene, homozygosity mapping, will take advantage of the availability of consanguineous Saudi Arabian pedigrees with multiple affected members. Strategies for initial gene localization will include: (i) allele-frequency dependent homozygosity mapping (AHM), (ii) a novel variation on AHM, using pooled DNA from affected and unaffected members for much more efficient genotyping, and (iii) genomic mismatch scanning (GMS) to screen for genomic regions that are identical by descent. Other traditional physical mapping approaches will be used for positional cloning. Mutation scanning detection methods will then detect specific mutations. Identification and cloning the PCG are critical to the study of eye development, to the institution of more appropriate therapies, and to the counseling of patients and families with PCG.